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A Saccharomyces cerevisiae mutant with increased virulence
Robert T Wheeler1, Martin Kupiec, Paula Magnelli
1Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02139,USA.
Summary
Saccharomyces cerevisiae, or bakers' yeast, can cause infections in immunocompromised individuals. A specific gene knockout (ssd1) significantly increases yeast virulence by altering cell surface characteristics and overstimulating immune responses.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Saccharomyces cerevisiae (bakers' yeast) is typically non-pathogenic in healthy individuals.
- Increasing isolation from immunocompromised patients necessitates understanding its virulence.
- Questions arise regarding the origin, survival, and virulence in human hosts.
Purpose of the Study:
- Compare the virulence of different Saccharomyces cerevisiae isolates in a mouse model.
- Investigate the role of the SSD1 gene in yeast virulence.
- Determine the mechanism by which altered yeast surface characteristics affect host immune response.
Main Methods:
- Infection of a mouse model with clinical, plant, and laboratory yeast strains.
- Genetic knockout of the SSD1 gene in yeast isolates.
- In vitro assessment of cytokine induction in macrophages.
Main Results:
- Plant isolate was lethal in mice; laboratory strain was avirulent.
- SSD1 gene knockout (ssd1 Delta/ssd1 Delta) increased virulence in clinical and plant isolates.
- Hypervirulent ssd1 Delta/ssd1 Delta strain potently elicited proinflammatory cytokines from macrophages.
Conclusions:
- Yeast virulence is strain-dependent and can be modulated by genetic factors like SSD1.
- Altered cell surface characteristics in ssd1 Delta/ssd1 Delta mutants enhance virulence.
- Overstimulation of proinflammatory responses by unique surface features contributes to increased yeast pathogenicity.